Vorolanib + Atezolizumab for Small Cell Lung Cancer

Overseen By Daniel Morgensztern

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Platinum, Etoposide, Atezolizumab

Must not be taking: NSAIDs, Glucocorticoids, Antiplatelets

Disqualifiers: Other malignancy, Untreated brain metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

11 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to determine whether adding vorolanib to atezolizumab will improve the length of time that participants are cancer-free after receiving standard chemotherapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on chronic antiplatelet therapy (like certain blood thinners) or high doses of systemic glucocorticoids (steroids). It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Vorolanib + Atezolizumab for Small Cell Lung Cancer?

Atezolizumab, when combined with chemotherapy, has been shown to improve survival outcomes in patients with extensive-stage small cell lung cancer, as seen in the IMpower133 trial. This combination is now considered a standard treatment option for this type of cancer. ^{1 2 3 4 5}

Is the combination of Vorolanib and Atezolizumab safe for humans?

Atezolizumab, used in combination with chemotherapy for small cell lung cancer, has been generally well tolerated in trials, with no new safety concerns beyond those known for the individual drugs. Common side effects include blood-related issues, skin rash, and low thyroid function, but it did not negatively affect patients' quality of life. ^{3 6 7 8 9}

How does the drug Vorolanib + Atezolizumab differ from other treatments for small cell lung cancer?

The combination of Vorolanib and Atezolizumab is unique because it combines a targeted therapy with an immune checkpoint inhibitor. Atezolizumab works by blocking PD-L1, a protein that helps cancer cells evade the immune system, thereby boosting the body's immune response against the tumor. This approach is different from traditional chemotherapy, which directly kills cancer cells but does not specifically enhance the immune system's ability to fight cancer. ^{1 2 5 6 10}

Research Team

Daniel Morgensztern

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Adults with extensive-stage small cell lung cancer who've had specific initial treatments without disease progression. They must have normal organ and bone marrow function, not be on certain blood thinners or antiplatelet drugs, and can't have uncontrolled high blood pressure or recent severe infections. Participants need to agree to use contraception and cannot be pregnant or breastfeeding.

Inclusion Criteria

You need to have a certain level of a type of white blood cell called neutrophils.

I agree to use birth control during and after the study and am not breastfeeding.

I've had 3-4 cycles of specific cancer treatment without my tumor growing and can start the study treatment within 6-8 weeks.

Exclusion Criteria

I do not have untreated brain metastases or brain bleeding, and I haven't had preventive brain radiation.

My high blood pressure has not been controlled with medication for over 3 weeks.

I have not coughed up a significant amount of blood recently nor does my cancer invade major blood vessels.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive 3 to 4 cycles of standard-of-care induction therapy

9-12 weeks

Maintenance Treatment

Participants receive atezolizumab intravenously every 3 weeks and vorolanib by mouth daily

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Atezolizumab
• Vorolanib

Trial Overview The trial is testing if adding vorolanib to atezolizumab extends the time patients remain cancer-free after standard chemotherapy. Patients will receive this combination as a maintenance therapy, which means it's used after initial treatment to help keep the cancer from coming back.

Participant Groups

Group I: Vorolanib + Atezolizumab Experimental Treatment 2 Interventions

Consenting and eligible participants who have no evidence of tumor progression after 3 to 4 cycles of standard-of-care induction therapy will receive atezolizumab intravenously (IV) every 3 weeks and vorolanib by mouth daily.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Xcovery Holdings, Inc.

Industry Sponsor

Trials

10

Recruited

620+

Xcovery Holding Company, LLC

Industry Sponsor

Trials

9

Recruited

530+

Findings from Research

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

In a phase 1 study involving 17 patients with relapsed or refractory small-cell lung cancer (SCLC), atezolizumab was generally well tolerated, with 64.7% experiencing any-grade treatment-related adverse events, the most common being fatigue.

Atezolizumab showed some antitumor activity, with a partial response in 5.9% of patients and a median overall survival of 5.9 months, suggesting potential benefits for patients with high T-effector gene signature and PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Chiang, AC., Sequist, LVD., Gilbert, J., et al.[2021]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

In a study of 518 patients with extensive small cell lung cancer (SCLC) receiving atezolizumab plus chemotherapy, the median overall survival was 11.3 months, with 46.7% of patients alive at 12 months, indicating the treatment's effectiveness in a real-world setting.

The study demonstrated that 23.6% of patients continued atezolizumab treatment beyond disease progression, suggesting a potential strategy for improving outcomes, particularly in patients with better performance status (PS 0/1) who had a median overall survival of 12.2 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study. Falchero, L., Guisier, F., Darrason, M., et al.[2023]

In a study of 47 patients with transformed small-cell lung cancer (T-SCLC), combining the PD-L1 inhibitor atezolizumab with chemotherapy resulted in a high objective response rate of 73% and significantly improved overall survival (20.2 months) compared to those who did not receive immunotherapy (7.9 months).

The combination therapy was well tolerated, showing a safety profile consistent with previous studies, suggesting it could be a promising treatment option for T-SCLC patients, particularly those with positive PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. Zhang, CY., Sun, H., Su, JW., et al.[2023]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

In a retrospective study of 213 patients with extensive-stage small cell lung cancer (SCLC), atezolizumab combined with chemotherapy demonstrated a median progression-free survival (PFS) of 6.8 months and overall survival (OS) of 11.9 months, confirming its efficacy in a real-life setting.

The treatment was generally safe, with manageable hematological side effects, and factors like ECOG performance status and number of metastatic sites were found to influence both PFS and OS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group. Gürbüz, M., Kutlu, Y., Akkuş, E., et al.[2022]

Atezolizumab, an inhibitor of PD-L1, was found to be well tolerated in a phase 1-2 trial involving 90 children and young adults with refractory or relapsed solid tumors, with no fatal adverse events reported.

While only 5% of patients achieved an objective response, the study showed comparable serum concentrations of atezolizumab between children and young adults, suggesting potential for future research into optimizing immune checkpoint inhibitors for specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. Geoerger, B., Zwaan, CM., Marshall, LV., et al.[2020]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study. [2023]

5. Ireland pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1-2 study. [2020]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]